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Subcutaneous immunotherapy suppresses Th2 inflammation and induces neutralizing antibodies, but sublingual immunotherapy suppresses airway hyperresponsiveness in grass pollen mouse models for allergic asthma
- Source :
- Clinical and Experimental Allergy, 48(8), 1035-1049. Wiley
- Publication Year :
- 2018
- Publisher :
- Wiley, 2018.
-
Abstract
- BackgroundBoth subcutaneous and sublingual allergen immunotherapy (SCIT and SLIT) have been shown to effectively suppress allergic manifestations upon allergen exposure, providing long-term relief from symptoms in allergic disorders including allergic asthma. Clinical studies directly comparing SCIT and SLIT report a different kinetics and magnitude of immunological changes induced during treatment. Comparative studies into the mechanisms underlying immune suppression in SCIT and SLIT are lacking.ObjectiveWe aimed to establish an experimental model for grass pollen (GP) SCIT and SLIT that would allow a head-to-head comparison of the two treatments.MethodsBALB/c mice were sensitized with GP extract, followed by SCIT and SLIT treatments with various GP dosages. Subsequently, we challenged mice with GP and measured airway responsiveness (AHR), GP-specific immunoglobulins, ear swelling tests (EST), eosinophilic inflammation in bronchoalveolar lavage fluid (BALF), and T cell cytokine release after restimulation of lung cells (IL-5, IL-10, and IL-13).ResultsWe find that SLIT treatment was able to suppress allergen-induced AHR, while allergic inflammation was not effectively suppressed even at the highest GP dose in this model. In contrast, SCIT treatment induced higher levels of GP-specific IgG1, while SLIT was superior in inducing a GP-specific IgG2a response, which was associated with increased Th1 activity in lung tissue after SLIT, but not SCIT treatment. Interestingly, SCIT was able to suppress Th2-type cytokine production in lung cell suspensions, while SLIT failed to do so.Conclusions and clinical relevanceIn conclusion, GP-SCIT suppresses Th2 inflammation and induced neutralizing antibodies, while GP-SLIT suppresses the clinically relevant lung function parameters in an asthma mouse model, indicating that the two application routes depend on partially divergent mechanisms of tolerance induction. Interestingly, these data mirror observations in clinical studies, underscoring the translational value of these mouse models.
- Subjects :
- 0301 basic medicine
tolerance induction
medicine.medical_treatment
grass pollen
0302 clinical medicine
Antibody Specificity
subcutaneous immunotherapy
Immunology and Allergy
medicine.diagnostic_test
biology
ANAPHYLAXIS
MURINE MODEL
Slit
Tolerance induction
Cytokine
IL-10
Cytokines
Pollen
Female
allergic asthma
Anaphylaxis
Allergen immunotherapy
Injections, Subcutaneous
Immunology
Administration, Sublingual
sublingual immunotherapy
Allergic inflammation
03 medical and health sciences
Th2 Cells
medicine
Respiratory Hypersensitivity
HOUSE-DUST MITE
Animals
mouse models
REGULATORY T-CELLS
House dust mite
business.industry
RHINITIS
Allergens
biology.organism_classification
medicine.disease
EFFICACY
Antibodies, Neutralizing
Asthma
Eosinophils
Disease Models, Animal
MICE
030104 developmental biology
Bronchoalveolar lavage
030228 respiratory system
Desensitization, Immunologic
Immunoglobulin G
business
Biomarkers
RESPONSES
Subjects
Details
- Language :
- English
- ISSN :
- 13652222 and 09547894
- Volume :
- 48
- Issue :
- 8
- Database :
- OpenAIRE
- Journal :
- Clinical and Experimental Allergy
- Accession number :
- edsair.doi.dedup.....982896e875e722ed205e1e09a0537dfb